Altered Liver Enzyme Markers in Patients with Asymptomatic, and Mild Omicron Infection: A Retrospective Study.

Purpose: The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections. Patients and Methods: A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0. Results: Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels. Conclusion: Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.

Correlation of patient symptoms with SARS-CoV-2 Omicron variant viral loads in nasopharyngeal and saliva samples and their influence on the performance of rapid antigen testing.

Evaluating SARS-CoV-2 viral loads in nasopharyngeal (NP) and saliva samples, factors affecting viral loads, and the performance of rapid antigen testing (RAT) have not been comprehensively conducted during SARS-CoV-2 Omicron epidemic. This prospective study included outpatients enrolled during Omicron variant period in Japan. Paired NP swab and saliva samples were collected to measure viral loads by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between viral loads and clinical symptoms was examined. The performance of an immunochromatography-based RAT kit was also assessed. A total of 153 patients tested within 3 days of symptom onset were included. The mean viral load was 5.60 log10 copies/test and 3.65 log10 copies/test in NP and saliva samples, respectively, resulting in a significant difference (P < 0.0001). Fever over 37°C (axillary temperature) and total number of symptoms other than fever were identified as independent factors positively correlated with the viral loads in both NP and saliva samples. RAT sensitivity using NP and saliva samples was 92% and 68%, respectively, using positive RT-qPCR results as the reference. The sensitivity of RAT using NP and saliva samples was significantly higher in patients with fever ≥37°C and/or at least one symptom than in those with fever <37°C and/or no symptoms (97% vs 83% in NP swabs; 80% vs 50% in saliva). Distinct symptoms, including fever ≥37°C, may reflect high Omicron variant viral loads. Rapid antigen testing, not only using nasopharyngeal swabs but also using saliva, would be useful for COVID-19 diagnosis as point-of-care testing, particularly for symptomatic patients. IMPORTANCE: We examined nasopharyngeal and salivary viral loads using samples collected from outpatients with SARS-CoV-2 infection during the Omicron epidemic in Japan and explored the outpatient factors correlated with viral loads. In addition, we evaluated the performance of an authorized rapid antigen testing (RAT) kit using nasopharyngeal and saliva samples with RT-PCR testing as the reference. Intriguingly, a correlation between fever and other symptoms and SARS-CoV-2 viral loads in nasopharyngeal and saliva samples was observed based on one COVID-19 outpatient visit. RAT sensitivity was influenced by viral loads. Nevertheless, nasopharyngeal RAT is considered useful for SARS-CoV-2 point-of-care diagnosis. In patients with distinct symptoms, including high-grade fever, salivary RAT could be a practical diagnostic tool because of the higher estimated viral loads. After the Omicron epidemic, outpatients with mild COVID-19 have become the main focus of diagnosis and treatment. Our study provides valuable information regarding the point-of-care diagnosis of these patients.

Impact of Diabetes Mellitus On In-Hospital Mortality of COVID-19 Patients in Japan Since COVID-19 Became a Common Infectious Disease.

AIM: The number of severe cases of coronavirus disease 2019 (COVID-19) has been decreasing since the emergence of the Omicron variant at the end of 2021. COVID-19 has become a common infectious disease in Japan and was downgraded to a category five infectious disease on May 8, 2023. This study aimed to compare the impact of diabetes mellitus on in-hospital mortality in COVID-19 patients since COVID-19 became a common infectious disease. PATIENTS AND METHODS: We conducted a retrospective observational study using data from an advanced critical care center in Osaka, Japan. The study included 1,381 patients of COVID-19 admitted to the center between March 1, 2020, and May 7, 2023, before COVID-19 became a category five infectious disease in Japan. Individuals younger than 18 years and pregnant women were excluded. We divided the patients into two groups: pre- and post-Omicron epidemic groups. The primary endpoint of the study was the in-hospital mortality, and the prognostic impact of diabetes mellitus was compared between the groups. RESULTS: The Kaplan-Meier curve showed a significantly lower rate of in-hospital mortality in the post-Omicron epidemic group than in the pre-Omicron epidemic group. The hazard ratio (HR) was 1.83 (95% CI, 1.36-2.50; p < 0.0001). Patients with diabetes mellitus had higher in-hospital mortality in both the pre- and post-Omicron epidemic groups; their HRs were 1.39 (95% CI, 1.21-1.59; p < 0.0001) and 1.45 (95% CI, 1.15-1.83; p = 0.0012), respectively. Diabetes mellitus had no significant interaction effect on the association between the post-Omicron epidemic and in-hospital mortality (p for interaction = 0.2154). CONCLUSION: Diabetes mellitus may continue contributing to COVID-19 in-hospital mortality in the future, as the Omicron sub-strain may still be prevalent.

Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort.

Objective: Monoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. Methods: CONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). Results: Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4-74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%-6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1-7) versus 8 (3-15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00-1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11-2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02-2.69, p = 0.041). Conclusions: MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening.

Clinical characteristics and risk factors of severe COVID-19 in hospitalized neonates with omicron variant infection: a retrospective study.

BACKGROUND: Reports on coronavirus disease 2019 (COVID-19) in neonates are limited, especially in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Omicron variant. This study aims to analyze the clinical characteristics and identify risk factors associated with severe COVID-19 in neonates infected with Omicron variant. METHODS: The study population was represented by neonates with COVID-19, who were admitted to The Affiliated Children's Hospital of Xi'an Jiaotong University in northwest China, from December 10, 2022 to January 20, 2023. Chinese Center for Disease Control and Prevention (CDC) announced that all local COVID-19 cases were infected with Omicron variant during the study period. Clinical and laboratory data were collected retrospectively. We used logistic regression analysis to investigate the risk factors for severe COVID-19, and derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: A total of 108 neonates, with median age of 18.1 days (interquartile range 9.4-23.0), were affected by COVID-19, of whom 84 had a mild disease, while 24 a severe one (22.2%). Of them, 6.5% were premature. No deaths were observed in the study population. The most common clinical manifestations were fever (88.9%) and cough (55.6%), with 5 cases (4.6%) complicated by pneumonia. 4 cases (3.7%) received respiratory support, including 2 cases of high-flow oxygen and 2 cases of continuous positive airway pressure. Gestational age at birth (OR: 0.615; 95% CI: 0.393-0.961), neutrophil count (NEU) (OR:0.576; 95% CI : 0.344-0.962) and lymphocyte count (LYM) (OR: 0.159; 95% CI: 0.063-0.401) were independent risk factors for severe COVID-19. The combination of NEU and LYM had the largest receiver operating characteristic area under the curve [0.912 (95% CI:0.830-0.993)] for identifying severe COVID-19, with a sensitivity of 0.833 and a specificity of 0.917. CONCLUSIONS: The general presentations and outcomes of neonatal COVID-19 caused by Omicron variant were not severe, and very few patients required respiratory support. The simultaneous decrease in NEU and LYM can be used to identify severe infection.

The Omicron Variant Is Associated with a Reduced Risk of the Post COVID-19 Condition and Its Main Phenotypes Compared to the Wild-Type Virus: Results from the EuCARE-POSTCOVID-19 Study.

Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020-June 2023); a subset of participants with ≥1 visit over the year after clinical recovery were analyzed. Variants were observed or estimated using Global Data Science Initiative (GISAID) data. Because patients returning for a post COVID-19 visit may have a higher PCC risk, and because the variant could be associated with the probability of returning, we used weighted logistic regressions. We estimated the proportion of the effect of wild-type (WT) virus vs. Omicron on PCC, which was mediated by Intensive Care Unit (ICU) admission, through a mediation analysis. In total, 1317 patients returned for a post COVID visit at a median of 2.6 (IQR 1.84-3.97) months after clinical recovery. WT was present in 69.6% of participants, followed by the Alpha (14.4%), Delta (8.9%), Gamma (3.9%) and Omicron strains (3.3%). Among patients with PCC, the most common manifestations were fatigue (51.7%), brain fog (32.7%) and respiratory symptoms (37.2%). Omicron vs. WT was associated with a reduced risk of PCC and PCC clusters; conversely, we observed a higher risk with the Delta and Alpha variants vs. WT. In total, 42% of the WT effect vs. Omicron on PCC risk appeared to be mediated by ICU admission. A reduced PCC risk was observed after Omicron infection, suggesting a possible reduction in the PCC burden over time. A non-negligible proportion of the variant effect on PCC risk seems mediated by increased disease severity during the acute disease.

Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5-11 years: a phase 2/3, randomized, active-controlled study.

Background: DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here. Methods: Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29. Results: Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off. Conclusions: Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years. Clinical trial registration: https://jrct.niph.go.jp/, identifier jRCT2031220665.

A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis.

BACKGROUND: The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns. Optic neuritis (ON) associated with Omicron infection and spontaneous demyelinating ON may manifest distinct disease progressions. This study aims to contrast the features of these two distinct etiologies of ON. METHODS: This case-control study comprised fifteen patients (21 eyes) diagnosed with Omicron infection-related ON and fifteen patients (24 eyes) with demyelinating ON serving as the control group. Clinical characteristics, cerebrospinal fluid (CSF) analysis, treatment protocols, and outcomes were compared between the two groups. RESULTS: The Omicron-infected group exhibited a higher incidence of pain upon ocular movement (p = 0.023) and peripapillary hemorrhages (p = 0.046). In CSF analysis, there was an elevation in white cell counts (WCCs) (p = 0.004), with lymphocytes being the predominant cell type in the Omicron-related ON group. However, oligoclonal bands (OCBs), indicative of intrathecal synthesis, were significantly lower and lagged behind those of the demyelinating ON group (p = 0.021). SARS-CoV-2 RNA was not directly detected in the CSF of the Omicron-related ON group, and the degree of WCC elevation was closely linked with peripapillary hemorrhages (odds ratio = 0.029, p = 0.02). Additionally, the Omicron-related ON group displayed more pronounced ganglion cell loss following 3-month treatment (p = 0.02). CONCLUSION: Omicron-related ON is distinguished by more pronounced clinical symptoms and distinct CSF characteristics compared to spontaneous demyelinating ON. The absence of viral RNA sequence in the CSF of Omicron-associated ON supports the use of steroid monotherapy; however, varying treatment options and prognoses should be considered for these two types of ON.

Risk of death in old Japanese COVID-19 cases infected with the Omicron variant: a population-based study.

We assessed case fatality rates (CFRs) in cases aged ≥70 years in 10 Japanese prefectures (14.8 million residents) diagnosed between January 2022 and March 2023, when the Omicron variant was dominant in Japan. We selected incident reports on 283,052 study subjects from participating Public Health Centers adhering to the Infectious Diseases Control Law. Cases were passively followed up until the end of their isolation, date of death or 28 days after the COVID-19 diagnosis, whichever occurred first. We calculated age-standardized CFRs with 95% confidence intervals (CI) using the Japanese population aged 70-79, 80-89 and ≥90 in 2022 divided into 16 subgroups according to the period of COVID-19 diagnosis. The total overall CFR was 1.59% (95% CI 1.55-1.64); it ranged between 0.67% (95% CI 0.38-0.96, May 23-June 19) and 2.58% (95% CI 2.36-2.80, January 31-February 27). We observed three peaks of age-standardized CFRs paralleling the 6th, 7th and 8th endemic COVID-19 waves driven by Omicron in Japan (2.2% January 31-February 27, 1.0% July 18-August 14 and 1.6% December 26-January 22, 2023, respectively). Population-based CFRs for Omicron variant COVID-19 in Japanese aged ≥70 years remained <3% throughout the period January 2022-March 2023, including during three large endemic waves in this country.

Comparative 60-day effectiveness of bivalent versus monovalent mRNA vaccines in Shelby County: a population-level analysis.

Background: Two monovalent mRNA vaccines, available in December 2020, were demonstrated to have high efficacy against both the original SARS-CoV-2 strain and variants circulating through the summer and into the fall of 2021. In the context of the Omicron/BA.1 variant, which was predominant from late fall 2021 into winter of 2022 in the United States, and subsequent Omicron subvariants that have been predominant thereafter, vaccine effectiveness of the monovalent mRNA vaccine option is attenuated. Objectives: We aim to investigate the relative effectiveness of the bivalent booster compared to the monovalent booster against SARS-CoV-2 infection in the 60 days following administration in Shelby County, TN. Design: This observational population-based cohort study utilizes COVID-19 surveillance data to identify adults who were vaccinated with a monovalent booster dose between August 1, 2022 and August 30, 2022 or a bivalent booster dose between September 1, 2022 and September 30, 2022. Both groups were followed for COVID-19 status for 60 days from their administration date. Methods: We calculated incidence rates with 95% confidence intervals and propensity-adjusted hazard ratios with 95% confidence intervals of COVID-19 diagnosis in the 60 days following administration of the booster dose between the bivalent group and the monovalent group. Stratified analysis was conducted by age group (18-34, 35-64, and 65+ years old). Results: The incidence of reported SARS-CoV-2 infection was substantially higher for those who received the monovalent booster, across age groups. Overall, we observed a 51% lower hazard of infection during the study period among those who received the bivalent booster, compared to the monovalent booster. Conclusion: These results support and extend prior findings that the bivalent booster dose may be more effective in preventing infection against the Omicron sub-variants of SARS-CoV-2.

Hematocrit and Albumin Levels at Admission Predict in-Hospital Mortality in Pediatric COVID-19 Omicron Variant Patients.

Introduction: The Omicron variant is the present predominant COVID-19 strain worldwide. Accurate mortality prediction can facilitate risk stratification and targeted therapies. The study aimed to evaluate the feasibility of the difference in hematocrit and albumin (HCT-ALB) levels, alone or combined with the pediatric Sequential Organ Failure Assessment (pSOFA) score and lactate level, to predict the in-hospital mortality of COVID-19 Omicron variant-infected pediatric patients. Methods: A multicenter retrospective cohort study was performed for children with COVID-19 Omicron variant infection between December 2021 and January 2022. The demographics, clinical characteristics, hospital admission laboratory test results, and treatments were recorded. The in-hospital mortality was documented. The associations between HCT-ALB levels and mortality, and between HCT-ALB+pSOFA+lactate and mortality were analyzed. Results: A total of 119 children were included. The median age was 1.6 (interquartile range: 0.5-6.2) years old. There were 70 boys and 49 girls. The mortality rate was 14.3% (17/119). The univariate and multivariate Cox regression analysis revealed that HCT-ALB was associated to in-hospital mortality (hazard ratio: 1.500, 95% confidence interval: 1.235-1.822, p<0.001). The receiver operating characteristic curve analysis revealed that HCT-ALB can be used to accurately predict in-hospital mortality at a cut-off value of -0.7 (area under the curve: 0.888, sensitivity: 0.882, specificity: 0.225, Youden index: 0.657, p<0.001). These patients were assigned into three groups based on the HCT-ALB level, pSOFA score, and lactate level (low-, medium-, and high-risk groups). The Kaplan-Meier analysis revealed that the mortality increased in the high-risk group, when compared to the medium-risk group (p<0.01). The latter group had a higher mortality, when compared to the low-risk group (p<0.01). Conclusion: The HCT-ALB level can be applied to predict the in-hospital mortality of children infected with the COVID-19 Omicron variant. Its combination with other variables can improve prediction performance.

The impact of vaccine type and booster dose on the magnitude and breadth of SARS-CoV-2-specific systemic and mucosal antibodies among COVID-19 vaccine recipients.

The COVID-19 pandemic has had a major impact on global health and economy, which was significantly mitigated by the availability of COVID-19 vaccines. The levels of systemic and mucosal antibodies against SARS-CoV-2 correlated with protection. However, there is limited data on how vaccine type and booster doses affect mucosal antibody response, and how the breadth of mucosal and systemic antibodies compares. In this cross-sectional study, we compared the magnitude and breadth of mucosal and systemic antibodies in 108 individuals who received either the BNT162b2 (Pfizer) or CoronaVac (SinoVac) vaccine. We found that BNT162b2 (vs CoronaVac) or booster doses (vs two doses) were significantly associated with higher serum IgG levels, but were not significantly associated with salivary IgA levels, regardless of prior infection status. Among non-infected individuals, serum IgG, serum IgA and salivary IgG levels were significantly higher against the ancestral strain than the Omicron BA.2 sublineage, but salivary IgA levels did not differ between the strains. Salivary IgA had the weakest correlation with serum IgG (r = 0.34) compared with salivary IgG (r = 0.63) and serum IgA (r = 0.60). Our findings suggest that intramuscular COVID-19 vaccines elicit a distinct mucosal IgA response that differs from the systemic IgG response. As mucosal IgA independently correlates with protection, vaccine trials should include mucosal IgA as an outcome measure.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes.

Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives.

The coronavirus disease 2019 (COVID-19) pandemic has sparked widespread concern globally, particularly with the Omicron variant and its sub-lineages emerging as the predominant cause of infection for nearly two years. Taiwan's successful containment of COVID-19, underscored by broad vaccine coverage, the utilization of anti-viral therapeutics, and timely response strategies, has resulted in reduced excess mortality. Moreover, there is a crucial need for a phased exit strategy, balancing efforts to curtail disease transmission with the mitigation of socioeconomic impacts from rigorous measures. In this review, we examined the evolution and the epidemiological landscape of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sub-variants in Taiwan as well as other countries of the world. We also critically evaluated the effectiveness of COVID-19 vaccines against various SARS-CoV-2 variants. Additionally, we addressed the advantages of heterologous immunization strategies, fluctuations in neutralizing antibody titers, and complexities in establishing protective correlates among swiftly mutating viral variants.

Chronic Obstructive Pulmonary Disease and the Omicron Variant of COVID-19 Prognosis: A Retrospective Cohort Study.

BACKGROUND AND AIM: This retrospective cohort study aimed to investigate the association between chronic obstructive pulmonary disease (COPD) and the prognosis of COVID-19 patients infected with the Omicron variant. The primary objective was to determine if COVID-19 patients with COPD had higher mortality rates compared to those without COPD. Secondary objectives included assessing the risk of respiratory failure, hospital stay length, intensive care unit (ICU) admission, and oxygen requirements in COPD patients with COVID-19. MATERIALS AND METHODS: The study included 2761 COVID-19 patients admitted to the Princess Margaret Hospital, Hong Kong, between January 1 and June 30, 2022. Among them, 7.4% (n = 205) had COPD. Demographic and clinical data, including vaccination status and comorbidities, were collected. The primary outcome was 30-day mortality, and secondary outcomes included respiratory support requirement, hospital stay length, and ICU admission. Logistic regression analyses were conducted, adjusting for potential confounders. RESULTS: COPD did not independently increase the risk of COVID-19 mortality after adjusting for confounders. Instead, older age, male sex, incomplete vaccination, long-term oxygen therapy use, and specific comorbidities were identified as significant predictors of 30-day mortality. COPD patients were more likely to require oxygen and noninvasive ventilation, but there were no significant differences in other secondary outcomes compared to non-COPD patients. CONCLUSION: COPD itself was not an independent risk factor for COVID-19 mortality. Age, sex, vaccination status, comorbidities, and long-term oxygen therapy use were important predictors of mortality. These findings underscore the importance of considering multiple factors when assessing the impact of COPD on COVID-19 prognosis, particularly with the Omicron variant.

The Impact of Long COVID on the Quality of Life.

Background and Objectives: The term long COVID refers to patients with a history of confirmed COVID-19 infection, who present symptoms that last for at least 2 months and cannot be explained by another diagnosis. Objectives: The present study aims to determine the most common symptoms of the long COVID syndrome and their impact on the quality of life. Materials and Methods: A prospective observational study was conducted on patients diagnosed with mild and moderate COVID-19 (based on a positive SARS-CoV-2 molecular diagnostic or rapid antigen test and severity form definition) at the Clinical Hospital of Infectious Diseases, Cluj-Napoca, Romania. Clinical examinations with detailed questions about symptoms were performed at the time of the diagnosis of COVID-19 and the six-month follow-up. Two years after COVID-19 infection, patients were invited to complete an online quality-of-life questionnaire regarding long COVID symptoms. Results: A total of 103 patients (35.92% males) with a mean age of 41.56 ± 11.77 were included in this study. Of the total number of patients, 65.04% presented mild forms of COVID-19. Data regarding the vaccination status showed that 83.5% were vaccinated against SARS-CoV-2. The most common symptoms at diagnosis were cough (80.6%), fatigue (80.4%), odynophagia (76.7%), and headaches (67.6%), with female patients being statistically more likely to experience it (p = 0.014). Patients with moderate forms of the disease had higher levels of both systolic (p = 0.008) and diastolic (p = 0.037) blood pressure at diagnosis, but no statistical difference was observed in the 6-month follow-up. The most common symptoms at 2 years (in 29 respondent subjects) were represented by asthenia (51.7%), headache (34.5%), memory disorders (27.6%), abdominal meteorism (27.6%), and arthralgia (27.6%). In terms of cardiovascular symptoms, fluctuating blood pressure values (20.7%), palpitations (17.2%), and increased heart rate values (17.2%) were recorded. Conclusions: If at the time of diagnosis, the most frequent manifestations of the disease were respiratory, together with headache and fatigue, at re-evaluation, asthenia, decreased effort tolerance, and neuropsychiatric symptoms prevailed. Regarding the cardiovascular changes as part of the long COVID clinical picture, some patients developed prehypertension, palpitations, and tachycardia.

Adult Outpatients with Long COVID Infected with SARS-CoV-2 Omicron Variant. Part 1: Oral Microbiota Alterations.

BACKGROUND: Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. METHODS: Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. RESULTS: One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). CONCLUSION: There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.

Wuhan Sequence-Based Recombinant Antigens Expressed in E. coli Elicit Antibodies Capable of Binding with Omicron S-Protein.

The development of cross-reactive vaccines is one of the central aims of modern vaccinology. Continuous mutation and the emergence of new SARS-CoV-2 variants and subvariants create the problem of universal coronavirus vaccine design. Previously, the authors devised three recombinant coronavirus antigens, which were based on the sequence collected in 2019 (the Wuhan variant) and produced in an E. coli bacterial expression system. The present work has shown, for the first time, that these recombinant antigens induce the production of antibodies that clearly interact with produced in CHO full-length S-protein of the Omicron variant. The immunogenicity of these recombinant antigens was studied in formulations with different adjuvants: Freund's adjuvant, Al(OH)3 and an adjuvant based on spherical particles (SPs), which are structurally modified plant virus. All adjuvanted formulations effectively stimulated Omicron-specific IgG production in mice. These universal coronavirus antigens could be considered the main component for the further development of broad-spectrum coronavirus vaccines for the prevention of SARS-CoV-2 infection. The present work also provides evidence that the synthetic biology approach is a promising strategy for the development of highly cross-reactive vaccines. Moreover, it is important to note that the bacterial expression system might be appropriate for the production of antigenically active universal antigens.

Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers.

We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.

Impact of corticosteroid doses on prognosis of severe and critical COVID-19 patients with Omicron variant infection: a propensity score matching study.

BACKGROUND: There is lack of research on corticosteroid use for severe and critical COVID-19 patients with Omicron variant infection. METHODS: This multi-center retrospective cohort study involved 1167 patients from 59 ICUs across the mainland of China diagnosed with severe or critical SARS-CoV-2 Omicron variant infection between November 1, 2022, and February 11, 2023. Patients were segregated into two groups based on their corticosteroid treatment-usual dose (equivalent prednisone dose 30-50 mg/day) and higher dose (equivalent prednisone dose > 50 mg/day). The primary outcome was 28-day ICU mortality. Propensity score matching was used to compare outcomes between cohorts. RESULTS: After propensity score matching, 520 patients in the usual dose corticosteroid group and 260 patients in the higher dose corticosteroid group were included in the analysis, respectively. The mortality was significantly higher in the higher dose corticosteroid group (67.3%, 175/260) compared to the usual dose group (56.0%, 291/520). Logistic regression showed that higher doses of corticosteroids were significantly associated with increased mortality at 28-day (OR = 1.62,95% CI 1.19-2.21, p = 0.002) and mortality in ICU stay (OR = 1.66,95% CI 1.21-2.28, p = 0.002). Different types of corticosteroids did not affect the effect. CONCLUSIONS: The study suggests that higher-dose corticosteroids may lead to a poorer prognosis for severe and critical COVID-19 patients with Omicron variant infection in the ICU. Further research is needed to determine the appropriate corticosteroid dosage for these patients.